How would you approach the treatment of patients with von Willebrand disease or hemophilia A previously managed with intranasal DDAVP during the recall?

There are two separate questions here, one is easy and one complicated. 

Desmopressin challenges can be performed with intravenous desmopressin, 0.3 mcg/kg. It is not necessary to challenge a patient with IV who previously responded well to the nasal preparation, in my view.  

How to approach treatment for either mild hemophilia A or VWD previously known to respond to nasal high dose desmopressin (Stimate(R)) is more of a conundrum. The shortage is likely to last more than a year. I find it helpful to think about all the possibilities before deciding what to do for individual patients. Formally, that list includes: 

• Forego hemostatic treatment (for bleeding) or prophylaxis (for procedures).
• Use intravenous desmopressin as per the label. 
• Use VWF-containing plasma-derived concentrates (for VWD) or recombinant factor VIII preparations instead.
• Use alternative hemostatic agents, if effective. For example, use tranexamic acid for menorrhagia, even if a woman has been using desmopressin as Stimate effectively.  
• Defer certain elective procedures. Here I am thinking about cosmetic or non-urgent dental work, for example, that might be deferred already because of the pandemic.

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Other considerations

Other #1: [Some have advocated the ability to use IV preparations of desmopressin subcutaneously, but I have not recommended this myself yet (October, 2020) and my understanding is that the US formulation of IV desmopressin is too low a concentration to make this practicable for larger individuals.]

Other #2: [There are rare mild hemophilia patients with past medical history of inhibitors, or strongly positive family history for inhibitors, or mutations at high risk of inhibitors, for whom IV factor VIII is NOT a safe alternative, these patients should receive IV desmopressin in my view.]  

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As one ponders these alternatives, I see little choice but to take each case individually and discuss the pros and cons with patients. The common thread of several of these is a significant nuisance factor of the unavailability of Stimate(R). Both IV desmopressin and factor products are safe, but they aren't readily used for monthly menstrual periods or routine dental prophylaxis. I don't think forgoing treatment for bleeding is prudent in many cases, but imagine a unilateral nosebleed that might have been cause for treatment in the other nostril with desmopressin as Stimate until the recall: if the bleeding stops on the way to the emergency department to get a dose of IV product, I might counsel a patient to try without.  

Take-home messages for me: 

1. The nuisance factor matters (a lot) to patients and providers, and the manufacturer needs to be encouraged to hurry up with the replacement factor. 

2. There are safe alternatives for emergency and non-emergency settings, both.  

3. The absence of this convenient non-blood-product therapy changes the risk-to-benefit ratio of certain procedures.  

Ellis Neufeld MD, PhD

St Jude Children's Research Hospital.